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Publication : REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis.

First Author  Ballas N Year  2005
Journal  Cell Volume  121
Issue  4 Pages  645-57
PubMed ID  15907476 Mgi Jnum  J:98945
Mgi Id  MGI:3580760 Doi  10.1016/j.cell.2005.03.013
Citation  Ballas N, et al. (2005) REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell 121(4):645-57
abstractText  Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its co-repressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli.
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